One of the greatest problems in the treatment of cancerous tumors is metastasis, i.e., the transmission of cells of a primary tumor to other locations in the patient and the establishment of new tumors at such locations. The spread of cancer cells from a primary tumor to a site of metastasis formation involves multiple interactions such as invasion of extracellular matrix, neovascularization, invasion of the blood vessel wall (intravasation), exit from the circulation (extravasation) and establishment of secondary growth. The complexity of the processes involved in metastasis has made it particularly difficult to develop effective treatments to inhibit or prevent the spread of metastatic cancer.
Moreover, metastasis is difficult to control because it often occurs before a primary tumor is diagnosed and treated and because the points of metastasis become multiple and therefore at some point impossible to treat by location-directed therapies such as radiation or surgery. Moreover, the metastatic lesions may be in locations which limit the possible dosages of the treatments, e.g., radiation, due to the sensitivity of the surrounding tissue to such treatments. Further, metastatic cells are heterogeneous, and cells which are resistant to conventional therapy tend to emerge.
Many current methods for identifying and validating anti-metastatic agents require that an investigator introduces a putatively therapeutic agent into a subject having a primary tumor and waits for metastatic tumors to arise, to determine if the agent inhibits metastases of the tumor. Waiting for a metastasis to develop is time-consuming, and the investigator cannot predict in advance where a metastasis will occur, and thus must monitor a variety of potential sites of metastasis. There remains a need to develop a rapid and efficient method to identify anti-metastatic agents and methods.